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Horm Metab Res 2003; 35(10): 602-606
DOI: 10.1055/s-2003-43507
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

The Prototypic Antidepressant Drug, Imipramine, but not Hypericum perforatum (St. John’s Wort), Reduces HPA-Axis Function in the Rat

P.  Frost 1 , S.  Bornstein 2 , M.  Ehrhart-Bornstein 2 , F.  O’Kirwan 1 , C.  Hutson 1 , D.  Heber 3 , V.  Go 3 , J.  Licinio 1 , M.-L.  Wong 1
  • 1Laboratory of Pharmacogenomics, Neuropsychiatric Institute, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
  • 2Department of Endocrinology, Heinrich-Heine University, Dusseldorf, Germany
  • 3Center for Dietary Supplement Research Botanicals, UCLA Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
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Publication History

Received 5 August 2002

Accepted after second revision 7 May 2003

Publication Date:
07 November 2003 (online)

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Abstract

Dysregulation in corticotropin-releasing hormone (CRH) secretion in the hypothalamus-pituitary-adrenal (HPA) axis may be involved in the etiology of major depressive disorder (MDD). Chronic therapy with standard antidepressant drugs, such as imipramine, can downregulate HPA axis function, indicating that the HPA axis may be an important target for antidepressant action. We tested several doses of a standardized commercial preparation of Hypericum perforatum plant extract (popularly known as St. John’s Wort), a medicinal herb used for treating mild depressive symptoms, to determine whether it also modulated HPA axis function. Chronic imipramine treatment (daily injections for 8 weeks) of male Sprague-Dawley rats significantly downregulated circulating plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone compared to animals treated with saline. However, chronic St. John’s Wort treatment (daily gavage for 8 weeks) had no effect on plasma ACTH or corticosterone, even at the highest doses tested. Our results confirm previous findings that imipramine may have significant peripheral HPA axis-mediated effects. However, our data does not support any role for H. perforatum in modulation of HPA axis function, suggesting that alternative pathways may be involved in mediating its antidepressant effects.

Key words

Major depressive disorder · Stress · ACTH · Corticosterone